Famciclovir Ameliorates Platelet Activation and Thrombosis by AhR-Regulated Autophagy

Abstract

Cardiovascular diseases (CVDs) and their severe complications have posed immense challenges to global healthcare systems. A significant obstacle in this field lies in the development of innovative targets, mechanisms, and drugs to mitigate the side effects associated with current antiplatelet therapies. Through screening relevant CVD targets in the Gene Card database, we found that AhR appears to be linked to CVDs. Computer-aided drug screening and molecular docking techniques identified famciclovir as a potential AhR inhibitor. Further experiments demonstrated that famciclovir suppresses AhR expression and platelet activation in thrombin-stimulated platelets, significantly reducing mitochondrial damage and oxidative stress. Notably, oral administration of famciclovir significantly inhibits thrombin-induced platelet aggregation without affecting coagulation factors or thrombolysis systems. Moreover, famciclovir mitigates FeCl₃-induced carotid arterial thrombosis and cerebral thrombosis induced by middle cerebral artery occlusion. Our study suggests that inhibiting AhR expression with famciclovir effectively reduces platelet activation and thrombosis, offering promise as a potential therapeutic strategy for improving CVDs.

Keywords: AhR; Famciclovir; Mitochondria; Oxidative stress; Platelet.